Human structural birth defects are often associated with physical or mental disability and are the leading cause of infant mortality in the US. The medical, economic, social, and family implications of birth defects are tremendous. For several decades the scientific community has stated that as many as 75% of birth defects have an unknown cause and only a small percentage of causes can be attributed to infections, environmental toxins, and a limited number of known genetic effects. Our limited knowledge regarding genetic (and nongenetic) factors that impact occurrence of most human birth defects is partly rooted in what has historically been a lack of data resources and limits on technology. We currently have an unprecedented opportunity to advance genomic research of birth defects. However, next steps toward capitalizing on such opportunities have obstacles. Primary among the obstacles is a lack of a coordinated interdisciplinary research agenda for the study of genetic etiologies and birth defects. In this application, we are proposing an initial effort towar solving such obstacles by having a 2-day workshop. The goal of the proposed workshop is to identify approaches and formulate strategies that are likely to have a substantial and sustained impact on discovering genomic and epigenomic risk factors for human birth defects. The workshop has been structured to optimize productive and engaging interactions between scientists with multiple point-counter point formal discussions on five pertinent topical areas. The meeting will assemble leading scientists from manifold disciplines including teratology, genetics, epidemiology, pediatrics, obstetrics, and molecular biology. The outcome of this meeting will be a comprehensive white paper that will characterize the discussions and provide a detailed prospectus for new research trajectories that can be broadly distributed.